PROJECT SUMMARY/ABSTRACT Due to the increase in poultry consumption nationally, the construction of mega-sized poultry feeding operations (PFO) in northeast Oklahoma is proceeding rapidly. The Oklahoma State Board of Agriculture approved a setback rule that imposes geographic restrictions on PFO. This rule, which is much less stringent than the previously proposed setback legislation, is not based on empirical exposure data. Since the rule went into effect on September 15, 2019, a substantial number of new PFO will be built, or existing PFO expanded, within a couple of years. Thus, an investigation of environmental health concerns in the affected community is urgently needed. The wave of new PFO construction that will ensue provides a time-sensitive opportunity for a baseline assessment of environmental exposures and microbiomes before the new PFO are stocked, followed by longitudinal post-assessments at critical times in the poultry raising cycle. PFO emit contaminants into the ambient atmosphere that can change the environmental and human nasal microbiome. The most common airborne contaminants emitted from poultry environments are ammonia and endotoxin, which is generated by production operations, manure storage, and land spreading of poultry litter. Ammonia is an odorous gas that results from the anaerobic decomposition of manure and carcasses. Numerous studies have found evidence that exposure to ammonia can irritate the eyes, nose, and mucous membranes in the upper respiratory tract, causing respiratory diseases. Similarly, endotoxin, the lipopolysaccharide part of the outer membrane of a gram-negative bacteria, is an odorless component that contributes to airway inflammation and plays a significant role in the adverse respiratory effects experienced in agricultural communities. Yet, the link between airborne contaminants from PFO and the related biological impact using a nasal microbiome have not been investigated in community-based participatory research. In this study, we will investigate the factors and mechanisms contributing to contamination levels to modulate the potential impact of PFO on residents' respiratory systems. Our central hypothesis is that living closer to a new PFO will be associated with a higher level of environmental exposure, which in turn will alter nasal microbiome patterns. The two goals of this time- sensitive R21 are 1) to assess levels of ammonia and size distribution of endotoxin particles in the air as a function of the resident's proximity to PFO and 2) to assess the interaction between the taxonomic community composition of the microbiota in the contaminated air and in the human nasal microbiome. The results of this study will enhance the current understanding of the mechanisms by which elevated levels of airborne contaminants from PFO alter the composition of the microbiota in air, eventually impacting respiratory health through changes in the composition and function of the nasal microbiome. The environmental metagenomics data longitudinally collected from this unique cohort will provide support for future studies using novel multi- omics approaches.